Vitamin D regulates the microbiota to induce optimal numbers of RORt/FoxP3+ regulatory T cells.

The active form of vitamin D (1,25(OH) 2 D) suppresses experimental models ofinflammatory bowel disease in part by regulating the microbiota. The role of vitamin D inthe regulation of microbe induced RORt/FoxP3+ T regs in the colon was determined.Vitamin D sufficient (D ) mice had significantly higher frequencies of FoxP3 T regsand RORt/FoxP3 T regs in the colon compared to vitamin D deficient (D−) mice. Thehigher frequency of RORt/FoxP3 T regs in D colon correlated with higher numbersof bacteria from the genus Clostridium XIVa and XVIII, and Bacteroides in D comparedto D- cecum. Transfer of the cecal bacteria from D or D- mice to germfree recipientsphenocopied the higher numbers of RORt/FoxP3 T regs in D versus D- recipientmice. The numbers of Clostridium XI, XIVa, and XVIII were correlated with thefrequencies of colonic RORt/FoxP3 T regs in the D and D- mice. D- mice with fewerRORt/FoxP3 T regs were significantly more susceptible to colitis than D mice.1,25D treatment of the D− mice beginning at 3 wks of age did not recoverRORt/FoxP3 T regs or the Clostridium XIVa and XVIII numbers to D values. Earlyvitamin D status shapes the microbiota to optimize the population of colonicRORt/FoxP3 T reg cells important for resistance to colitis.